Tear film measurement

ABSTRACT

The disclosure comprises a method for measuring the relative thickness of the lipid layer component of the precorneal tear film on the surface of an eye after distribution of the lipid layer subsequent to blinking. Light is directed to the lipid layer of a patient&#39;s eye with an illuminator. The illuminator is a broad spectrum light source covering the visible region and is a lambertion light emitter such that the light source is specularly reflected from the lipid layer and undergoes constructive and destructive interference in the lipid layer. The specularly reflected light is collected and focused using a collector such that the interference patterns on the tear film lipid layer are observable. The collector also produces an output signal representative of the specularly reflected light suitable for further analysis, such as projection on to a high resolution video monitor or analysis by or storage in a computer.

RELATED APPLICATION

This application is a Continuation-In-Part of U.S. patent applicationSer. No. 11/820,664 filed Jun. 20, 2007 now U.S. Pat. No. 7,758,190.

FIELD OF THE INVENTION

This invention relates generally to the field of measurement of the tearfilm thickness on the precomeal surface of the eye and moreparticularly, to the measurement of the thickness of the outermost layerof the tear film, i.e., the lipid layer.

BACKGROUND OF THE INVENTION

The human precomeal tear film is comprised of three primary layers, eachof which serves a specific function. The innermost layer of theprecomeal tear film provides a protective environment for thesuperficial epithelial cells of the cornea and helps protect againstmicrobes and foreign bodies. The outer surface of the precomeal tearfilm is the primary refracting surface of the eye. Its surface tensionhelps to smooth this surface, thus improving the optical quality of theimage ultimately impacting the retina. Additionally, the precomeal tearfilm provides a lubricating function during blinking. These structuresare often disrupted in dry eye conditions, which are some of the mostcommon ophthalmic disorders seen by eye-care practitioners. Dry eyedisorders and/or disease can lead to premature breakup of the tear filmafter a blink, leading to damage of the superficial epithelium which mayresult in discomfort and be manifested as optical blur. In addition, theability of a patient to wear contact lenses is a direct function of thequality and quantity of the tear film, and dry eye disorders and/ordisease therefore has a significant impact on contact lens wearparameters.

The precomeal tear film is comprised of an inner mucin layer, a middleaqueous layer, and an outermost thin lipid layer. Various treatments areused in an attempt to alleviate dry eye symptoms. For example, it hasbeen proposed to treat certain dry eye conditions by the application ofheat and pressure to unclog meibomian glands, or with pharmaceuticalmethods to unclog meibomian glands and to stimulate tear production.

Notwithstanding the foregoing, it has been a long standing and vexingproblem for clinicians and scientists to objectively demonstrate animprovement in the precomeal tear film thickness at the conclusion ofthe proposed treatment. Further, many promising treatments for dry eyehave failed to receive approval from the United States Food and DrugAdministration due to the inability to demonstrate clinicaleffectiveness to the satisfaction of the agency.

In response to the foregoing long felt need, various methods ofmeasuring the thickness of the precomeal tear film, and specifically thelipid layer thereof have been proposed. For example, Korb, one of theinventors of this invention provided an overview and background of hisinvention of a specular reflection microscope system that allowedquantification of the tear film lipid layer thickness based on theinterference colors of the lipid layer. This system included ahemi-cylindrical broad spectrum illumination source with heat absorbingfilters, a binocular microscope with a Zeiss beam-splitter providing 70%light to a high resolution video camera, a VHS recorder, and a highresolution 20-inch color monitor. Following calibration with EastmanKodak color reference standards (Wratten filters), the static anddynamic appearance of the lipid layer was observed before and afterblinking. During the observation period, the subject was instructed toblink naturally while gazing at a fixation target. For purposes ofquantization and standardization, a specific region of the tear film wasdesignated for analysis. This area encompassed a zone approximately onemm above the lower meniscus to slightly below the inferior pupillarymargin, averaging 7-8 mm wide and 2.5 mm in height. The dominant colorof the specularly reflected light within this designated area was usedas the basis for assigning lipid layer thickness values. Thicknessvalues were assigned to specific colors on the basis of prior work ontear film lipid layer interference colors (McDonald, 1969; Nom.; 1979;Guilon, 1982; Hamano et al., 1982) and are summarized in Table 1. Toconfirm the lipid layer thickness values assigned to each subject's tearfilm lipid layer, recordings were independently graded by two observersmasked as to subject identity. (Korb, D R, Baron D F, Herman J P, etal., Tear Film Lipid Layer Thickness as a Function of Blinking, Cornea1994:13:354-9). While the foregoing apparatus was effective in measuringimproved lipid layer thickness, measurement inaccuracies werenevertheless introduced into the system. Working backwards, the colormonitor had to be provided with a sufficient input signal to enable thelipid layer to be imaged on to the monitor screen. The foregoing thusrequired a minimum illumination to be provided to the slit lamp, ofwhich 70% was directed to the high resolution video camera. This, inturn, dictated the minimum amount of light required to illuminate thecorneal surface. Thus, the amount of light required to make theforegoing system operational was not optimum as it interfered with thenaturally occurring tear film as the heat generated by the light causedtear film evaporation. Further, the amount of light required to make thesystem functional caused some degree of reflex tearing.

Another apparatus for measuring the tear film is disclosed in EuropeanPatent Application EP 0 943 288 assigned to Kowa Company, Ltd. of Japan.The application discloses an apparatus for the non-contact measurementof the quantity of lacrimal fluid collected on the lower eyelid.According to the invention, tear volume is calculated from a measurementof the volume of fluid pooled at the lid eye meniscus. While knowledgeof the total volume of fluid may be of some use to eye-carepractitioners, it does not specifically measure the lipid layerthickness or its improvement as the result of a particular treatmentregimen.

U.S Pat. No. 4,747,683 to Marshall G. Doane discloses a Method andDevice for in Vivo Wetting Determinations wherein a contact lens isilluminated with coherent light and the pre-lens tear film is imaged insuch a way as to form an interference pattern. The image formed therebyis recorded and the tear film thickness is determined by correlating theinterference bands of the recorded image. A coherent light source and acamera are focused at the pre-lens film to image specularly reflectedlight from the front and rear surfaces of the tear film. A film motionanalyzer provides numerical coordinates of interference bands, and amicroprocessor analyses the coordinates to provide a quantitativemeasure of lens position or wetting characteristics. Again, whileknowledge of the tear film thickness covering the contact lens surfacemay be useful in the context of contact lens fitting, the Doaneapparatus does not specifically measure lipid layer thickness on thenatural eye.

Another instrument that purports to measure tear film lipid layerthickness is the Tearscope Plus manufactured by Keeler Instruments Inc.,of Broomall, Pa. and Berkshire, UK. More specifically, the Tearscope isa hand-held or slit lamp mounted device that comprises a tubular housingwhich contains a coaxially mounted cylindrical light source. Theinterior bore of the housing is covered with a cylindrical diffuserplate that diffuses the light. In use, the eye-care practitioner placesone end of the tube proximate the patient's eye thus illuminating thewhole eye, including the pupil, and observes the interference patternson the pupil surface through the opposite end of the tube. The color ofthe interference pattern generated by blinking is then correlated totear film thickness. The Tearscope is not without its inherent drawbacksand deficiencies as the process by which the eye is illuminated and themeasurement is made introduces error which is diagnosticallyunacceptable. For example, the proximity of the illuminator to the eyesurface when combined with the light intensity required to obtain aviewable interference pattern can cause reflex tearing. In addition, theillumination system employed illuminates the entire eye, including thepupil. Thus, light from the Tearscope is directed on to the retinalsurface which, in turn causes a proprioceptive response which also skewsmeasurement accuracy.

In view of the foregoing, it is an object of the present invention toprovide a method and apparatus that overcomes the drawbacks anddeficiencies of the prior art.

Another object of the present invention is to provide a method andapparatus that allows the accurate measurement of the thickness of thelipid layer component of the precorneal tear film.

A further object of the present invention is to provide a method andapparatus wherein the lipid layer thickness of the precorneal tear filmmay be measured without the introduction of reflex tearing.

A still further object of the present invention is to provide a methodand apparatus that enhances contrast and thereby the observability andmeasurablity of the lipid layer thickness of the precorneal tear film.

Yet another object of the present invention is to provide a method andapparatus for measuring the lipid layer thickness of the precorneal tearfilm using a low level of light in order to minimize tear filmevaporation that can alter the measurement.

Another object of the present invention is to provide a method andapparatus for measuring the lipid layer thickness of the precorneal tearfilm wherein the patient is comfortable during the examination.

Another object of the present invention is to provide a method andapparatus for measuring the lipid layer thickness of the precorneal tearfilm that minimizes light entering the pupil to minimize reflex tearingand proprioceptive responses that can alter the measurement.

SUMMARY OF THE INVENTION

In accordance with the foregoing, the invention comprises a method formeasuring the thickness of the lipid layer component of the precornealtear film on the surface of an eye after distribution of the lipid layersubsequent to blinking. Light is directed to the lipid layer of apatient's eye by use of an illuminator which produces specularlyreflected light rays. The illuminator is a broad spectrum, large arealambertian light source covering the visible region, the rays of whichare specularly reflected from the lipid layer and undergo constructiveand destructive interference in the lipid layer. The specularlyreflected light is collected and focused such that the interferencepatterns on the tear film lipid layer are observable. An output signalis produced that is representative of the specularly reflected lightwhich is suitable for further analysis, such as projection on to a highresolution video monitor or analysis by or storage in a computer.Alternatively, the interference patterns of the specularly reflectedlight may be directly observed by the clinician and recorded. In orderto facilitate ease of measurement, the patient's head may be positionedon an observation platform, for example, a slit lamp stand, when theilluminator directs light to the lipid layer of the patient's eye.

In a first embodiment of the invention, the illuminator is sized to showthe interference pattern of the lipid layer over the whole eye, (termedherein the “whole eye illuminator”), with the provision that theintensity of the light entering the pupil and striking the retina arebelow the threshold at which appreciable measurement error isintroduced, i.e., the reflex tear and proprioceptive responses are notactivated. Observation of the interference pattern in the preferredembodiment is through an opening in the illuminator.

In a second embodiment of the invention, the illuminator is sized toshow the interference pattern of the lipid layer below the pupil,(termed herein the “half eye illuminator”), such that the intensity ofthe light entering the pupil is extremely low, thus avoiding theintroduction of virtually all system-induced inaccuracy. Observation ofthe interference pattern in this second embodiment is from above theilluminator.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features will be understood with reference to thefigures, in which

FIG. 1 is a side view of the tear film analyzer according to the presentinvention mounted to a stand with a patient positioned for viewing ofinterference fringes on the lipid layer of the eye. The illuminatorportion is shown as a vertical cross section through the center.

FIG. 2 is a plan view of the tear film analyzer according to the presentinvention mounted to a stand with a patient positioned for viewing ofinterference fringes on the lipid layer of the eye.

FIG. 3 a is a side view of a second embodiment of the tear film analyzeraccording to the present invention mounted to a stand with a patientpositioned for viewing of interference fringes on the lipid layer of theeye. The illuminator portion is shown as a vertical cross sectionthrough the center.

FIG. 3 b is a side view of the second embodiment of the tear filmanalyzer according to the present invention mounted to a stand andtilted with a patient positioned for viewing of interference fringes onthe lipid layer of the eye. The illuminator portion is shown as avertical cross section through the center.

FIG. 4 a is a plan view of the second embodiment of the tear filmanalyzer according to the present invention mounted to a stand with apatient positioned for viewing of interference fringes on the lipidlayer of the eye.

FIG. 4 b is a plan view of the second embodiment of the tear filmanalyzer according to the present invention mounted to a stand andtilted with a patient positioned for view of interference fringes on thelipid layer of the eye.

FIG. 5 a is a plan view of the second embodiment of the tear filmanalyzer according to the present invention illustrating the illuminatorsurface that produces the outer edges of the viewable area ofinterference fringes.

FIG. 5 b is a side view of the second embodiment of the tear filmanalyzer according to the present invention illustrating the illuminatorsurface vertically positioned below the plane of the pupil and showingthe outer edges of the viewable area of interference fringes.

FIG. 5 c is a side view of the second embodiment of the tear filmanalyzer according to the present invention illustrating the illuminatorsurface positioned below the plane of the pupil and tilted at an angleand showing the outer edges of the viewable area of interferencefringes.

FIG. 6 is a perspective view, partially exploded, of the full eyeilluminator according to the present invention.

FIG. 7 is a plan view, sectioned horizontally through the center of theviewing hole of the full eye illuminator according to the presentinvention.

FIG. 8 is an end view, sectioned vertically through the center of thefull eye illuminator according to the present invention.

FIG. 9 is a perspective view, partially exploded of the half eyeilluminator according to the present invention.

FIG. 10 is a plan view with the top removed of the half eye illuminatoraccording to the present invention.

FIG. 11 is an end view, sectioned vertically through the center of thehalf eye illuminator according to the present invention.

FIG. 12 is a front view of the surface of an eye and illustratingschematically the area defined by the extreme lambertion rays whereininterference patterns are viewable.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

While the present invention will be described more fully hereinafterwith reference to the accompanying drawings, in which particularembodiments are shown, it is to be understood at the outset that personsskilled in the art may modify the invention herein described while stillachieving the favorable results of this invention. Accordingly, thedescription which follows it to be understood as a broad teachingdisclosure directed to persons of skill in the appropriate arts and notas limiting upon the present invention.

In a first embodiment best shown in FIGS. 1, 2 and 6-8, referred toherein as the “full eye illuminator”, the present invention broadlycomprises illuminating the lipid layer of the patient's eye andobserving the light specularly reflected therefrom. A second embodimentbest shown in FIGS. 3 a, 3 b, 5 a-5 c and 9-11, referred to herein asthe “half eye” illuminator is shown. The mode of operation of the twoembodiments is substantially identical and they will therefore bedescribed together using the same reference numerals and wheredifferences between the embodiments occur, they will be discussed.

The lipid layer of a patient's eye is illuminated with an illuminator100 and comprises a large area broad spectrum light source covering thevisible region. The illuminator 100 is a lambertian emitter adapted tobe positioned in front of the eye on a stand 300. As employed herein theterms “lambertion surface” and “lambertian emitter” are defined to be alight emitter having equal intensity in all directions. The light sourcecomprises a large surface area emitter, arranged such that rays emittedfrom the emitter are specularly reflected from the lipid layer andundergo constructive and destructive interference in the lipid layer. Animage of this surface is the backdrop over which the interference imageis seen and it should be as spatially uniform as possible. Theilluminator 100 illuminates a large area of the face which creates a 2.5mm high by 5 mm long viewable area centered beneath the pupil 310 (seeFIG. 12) which is adequate for lipid layer thickness determination andcorrelation to dry eye. By “viewable area” it is meant the active areathat satisfies the criteria for viewing interferences fringes; i.e.,approximately 2.5 mm×7 mm for the half eye illuminator. Full-eyeillumination, excluding the pupil area, reveals additional informationabout the whole eye pattern of lipid distribution.

The geometry of the illuminator 100 can be most easily understood bystarting from the camera lens and proceeding forward to the eye and thento the illuminator. The fundamental equation for tracing ray lines isSnell's law:N₁ Sin ø₁=N₂ Sin ø₂,   1)where N is the refractive index of the medium containing the ray, and øis angle of the ray relative to the normal from the surface. For areflected ray that doesn't enter the lipid layer, N₁=N₂, andø₁=ø₂   2)Under these conditions, Snell's law reduces to the classical “angle ofincidence is equal to the angle of reflectance” statement.

According to the present method, it is necessary to determine only theextreme rays (the ones at the outermost boundary of the desired viewingarea) to define the area of the illuminator. Since the surface of thatportion of the eye to be examined is approximately spherical, a linedrawn from the camera lens (or the observer's eye) to the edge of theviewing area on the observed eye will reflect at the same angle on theother side of the line normal to the eye surface at the point ofintersection of the line with the eye. When the half eye illuminatorused, it may be tilted to better accommodate the nose and illuminate alarger area of the inferior lipid layer. Notwithstanding the foregoing,experimentation using the half eye illuminator has shown that a tilt of10° to as much as 30° is still functional. Returning now to the full eyeilluminator, as best shown in FIGS. 1 and 2, it will be seen that facialfeatures block some rays from reaching the surface of the eye. The nose,cheeks, eyebrows, and eyelids block rays, causing shadows on the eyesurface. Positioning the illuminator for maximum area exposure is uniqueto each patient's facial structure. The mechanical dimensions (heightand width) of the illuminator may be extended to cover the biometricrange of facial features of the target population.

The illuminator 100 is a broad spectrum light source covering thevisible region between about 400 nm to about 700 nm. In the model thatwas constructed, high efficiency, white Light Emitting Diodes (“LEDs”)120 were used that have a 50° forward projection angle, 2500 mcd typicalintensity, and 5 mm diameter (part number NSPW510CS, available fromNichia Corporation, Wixom, Mich.). Other LEDs could be added to thepresent invention to enhance the spectral width in the near UV or nearIR regions. The light emitting array platform 130 (FIGS. 6, 7) intowhich the LEDs are mounted had a curved surface, subtending an arc ofapproximately 130° from the optical axis of the eye (see FIG. 5 a).Approximately 96 LEDs spaced apart in a grid pattern with 6 rows and 16columns were connected in parallel/series combinations and connected toan appropriate power supply, well known to those skilled in the art andtherefore, not shown. A housing is formed around the LED array platform130 by a pair of side panels 135, bottom and top panels 140, rear panel145 and the diffuser means or diffuser 150. The respective diffuser 150,LED platform 130, and rear panel 145 are flexible and fit within grooves147 located in the top and bottom panels 140 and the end pieces 135. Theentire assembly is snapped together and the side panels 135 are thenscrewed to top and bottom panels 140. While the illumination means 100illustrated in the figures is curved or arcuate and has a radius of7.620 inches from the center of the eye under examination, it could beflat as long as it subtends 130° around the eye. A curved surface ismore efficient in doing this, as the geometry yields a smaller devicewhich is easier for the practitioner to use in a clinical setting.

The total power radiated from the illuminator 100 must be kept to aminimum to prevent accelerated tear evaporation. In addition, aircurrents generated by heating or cooling systems can also cause excessevaporation and must be minimized (preferably eliminated) to maintainmeasurement accuracy. The brightness, or intensity, measured in μW/mm²,entering the pupil can cause reflex tearing, squinting, and other visualdiscomforts, all of which affect measurement accuracy. For a full-eyeilluminator, the curved lambertian emitter includes a centrallypositioned hole defining an opening 160 through which the means forcollecting and focusing the specularly reflected light, i.e., a camera,eye, or other lens 200, is positioned. The opening 160 in the centersubstantially prevents direct illumination from entering the pupil ofthe test eye. While less than optimal, the opening 160 could be locatedin other parts of the illuminator. The other eye, however, has the fulllight intensity entering the pupil. If the illumination intensity is lowenough, the exposed eye does not react. The exposed eye may also beoccluded with a mask, or the illuminator may be segmented so that partsof the surface are not illuminated. The half-eye illuminator stops belowthe centerline of the eye and does not directly illuminate either pupilor stated otherwise, light rays can only enter the pupil obliquely anddo not impinge on the retina. The current full-eye illuminator has abrightness or illumination intensity of between about 3 μW/mm² and 15μW/mm² with about 4.5 μW/mm² at the surface of the illuminator beingpreferred, which is held 1-2 inches from the eye. The total radiatedpower is less than 1 W and preferably no more than 400 mW. Brightnessabove about 6 μW/mm² becomes uncomfortable to the second eye if itenters the pupil so as to impinge directly on the retina. The frontsurface of the illuminator is the lambertian emitter, i.e., all pointson the extended illuminator surface are lambertian emitters, andcomprises a flexible white translucent acrylic plastic sheet 150approximately 1/16 inch thick that serves the function of diffusing thelight emitted from a plurality of LED point sources and transformingthem into the uniform Lambertian emitter.

In order to prevent alteration of the proprioceptive senses and reduceheating of the tear film, it is important to minimize the incident powerand intensity on the eye and thus, the step of collecting and focusingthe specularly reflected light is carried out by a high sensitivitycolor camera 200. The video camera, slit lamp or other observationapparatus 200 is positioned in opening 160 and is also mounted on stand300 as shown in FIG. 2 or in the case of the half eye illuminatorpositioned above the emitter as per FIGS. 3 a and 3 b. Detailedvisualization of the image patterns requires collecting the specularlyreflected light and focusing the specularly reflected light such thatthe interference patterns from the lipid layer are observable. Gooddigital imaging requires a CCD video camera having a resolution of up to1280×1024 pixels and at least 15 Hz frame rate to show the progressionof lipid interference patterns as they spread across the eye. The AVTDolphin 145C, ⅔ inch, CCD camera with 6.45 μm square pixels meets therequirements and outputs a signal representative thereof which may serveas the input signal to any one of a number of devices such as a videomonitor (preferably high resolution) or a computer for analysis and/orarchiving purposes.

The lens system employed in the instant tear film analyzer images a15-40 mm dimension in the sample plane (the eye) onto the active area ofthe CCD detector (e.g. 13 mm horizontal dimension for a ⅔ in. CCD). Thelens f-number should be as low as practical to capture maximum light andminimize the illumination power needed for a good image. The lens chosenfor the half-eye and full-eye systems is the Navitar Zoom 7000 closefocus zoom lens for ⅔in. format CCDs. At lower magnification (25-40 mmfield of view), the eye and lids can be examined to observe therelationship of the blink to the lipid layer thickness. A more detailedanalysis of the lipid layer can be obtained with a slightly highermagnification showing a 15-25 mm field of view.

The lipid layer thickness is not uniform and is classified on the basisof the most dominant color present in the interference pattern. It isbelieved that the lipid layer for most individuals cannot exceed 180 nm,and since thicker lipid layers provide better protection fromevaporation than thinner lipid layers, thicker lipid layers providegreater protection against the development of dry eye states. Thinnerlipid layers are associated with dry eye states and dry eye symptoms,particularly if the lipid layer thickness is less than 75 nm.

The present system displays the interference patterns from white lightincident on the lipid layer film. The relation between the colors of theinterference pattern and the lipid layer thickness (LLT) are shown inTable 1.

TABLE 1 LIPID LAYER Color THICKNESS (nm) Letter Grade Blue 180 A Blue/Brown 165 A− Brown/Blue 150 B+ Brown 135 B  Brown/Yellow 120 B−Yellow/Brown 105 C+ Yellow 90 C  Grey/Yellow 75 C− Grey 60 D+ Grey/White45 D  White 30 F 

Extensive research has established that thicker films are indicated by ablue and brown color, mid-thickness films are indicated by a yellowcolor, thinner films are indicated by a grey-yellow color, and very thinfilms exhibit a gray scale of different densities with whiterepresenting the thinnest. It is believed in color photometry, brown canbe obtained in an additive process by mixing small intensities of redand green, or orange and blue, basically the opposite ends of thevisible light spectrum. Alternatively, brown can be obtained in asubtractive process by filtering out the central yellow-green colorsfrom the white spectrum, leaving a blue-orange mix.

It has not been verified why the wavelengths of light observed in theinterference film are inverse to the film thickness, but extensiveclinical testing has led the inventors to the belief and the theory thatdestructive interference is the dominant process. The closer thewavelength is to the film thickness, the greater the interference, soyellow-red interference will have the strongest effect in a thickerfilm. However, thicker films appear blue, so it is postulated that redwavelengths are removed from the incident light spectrum by destructiveinterference and the reflected light appears blue.

For a thinner film, blue will have a stronger interference. Since thethinner films appear reddish, it is assumed that the blue is removed bydestructive interference. From this, we assume that the color seen isthe broadband surface reflection with the dominant interference colorband removed. That is, interference subtracts the portion of thespectrum indicative of the film thickness from the reflected light,leaving the complementary colors. This is the best explanation known tothe inventors of how brown is obtained from a system of this type. Itmust be noted that the thickness of the lipid layer on the eye is muchsmaller than all the wavelengths of visible light. Therefore, fullwavelength interference patterns are believed not to be possible. Forfractional wavelengths, (λ/2n, n=1,2 . . . ) the intensity in theinterference pattern decreases rapidly as n increases and the ability todifferentiate weak interference patterns from the background decreasesaccordingly.

When the lipid film thickness falls below about 90 nm, no color is seenin the image generated by the present apparatus (employing the currentLED light source), only gray of varying density. It is presumed thatviolet and ultraviolet interference effects predominate at thisthickness, but since they are absent from the incident spectrum, nocolor can be seen. Any interference remaining over the visible lightspectrum is so weak due to the very small fraction (λ/2n, n>5) thatfull-spectrum reflection and absorption effects dominate and noparticular color can be seen. Broadband destructive interference in the60-75 nm layers gives way to broadband constructive interference at thethinnest layer (<=30 nm).

In summary, it is believed that the present invention demonstrates theresults of subtractive colors, where subtracting the blue end from whitelight leaves a reddish tint, subtracting the center (yellow-green) fromthe spectrum leaves a brownish tint, and subtracting orange-red leaves ablue tint. Because all the interference patterns are fractionalwavelengths, and therefore relatively weak in intensity, the images arenot strongly saturated. Image enhancement techniques therefore assume ahigher importance for good visibility. Film thickness below about 90 nmcan be determined by gray scale analysis.

Should the use of real time or high speed data transfer and largestorage volumes be required for a given application, the use of a meansfor recording the output signal representative of the specularlyreflected light (video output signal) such as a high performancecomputer system would be needed. As employed herein, the term “realtime” is defined as data transfer, storage and retrieval at a raterequired for image generation that the observer requires for asubjectively satisfactory viewing experience. For viewing the motion ofthe lipid layer interference pattern after blinking a minimum of about15 frames per second is satisfactory for seamless motion perception.Depending upon settings, the camera can create 1.4-3.9 MB images at 15per second, or 21-57 MB/sec which must be processed by the computer forstorage, display, or computation. At this rate, one minute of recordingrequires 1.26-3.42 GB of storage. Given the presently availabletechnology, it is not reasonable to store recording sessions in RAM, sothe data from the camera must be streamed directly to a storage systemsized to meet the anticipated volume of data. For example, 500 GB ofstorage could record 147-397 tests of one minute duration. Various formsof data management could be applied to reduce the storage requirements,including image size, compression, and minimizing recording timeadequate to good diagnostics.

The software to operate the camera, capture the images, store andretrieve image files, and execute chosen calculations on the data iscritical to the success of the system. Relevant specifications are:

The mechanical system consists of components to position the patient'shead, position the illuminator and camera, focus the camera, and switchposition between eyes.

Current ophthalmic chin rests are adequate for positioning andrestraining the head. They include vertical (Z axis) adjustment.

A movable frame positions the camera and illuminator opposite thepatient's face. The illuminator and camera move together in a grossmanner, but the illuminator has an independent X and rotational motionsfor accommodating different facial geometries. Switching from eye to eyerequires moving the whole camera/illuminator frame away from thepatients face (X motion) and horizontally to line up with the second eye(Y motion). Focusing the camera requires fine control of X motion, andvertical Z motion is required to accommodate differences in patient eyepositions. A classical slit lamp biomicroscope stand incorporates mostof these motions, and have added angular motions not needed in thepresent system.

FIGS. 1, 2, 3 a-3 b illustrate the full-eye system. A typicalexamination session proceeds as follows:

-   -   Presets: The vertical relationship between the camera and the        illuminator is set. For a half-eye illuminator, the camera        position is just enough higher than the illuminator top edge        that the image contains no edge effects. When using the full-eye        illuminator, the camera is positioned coaxially with the hole        through the illuminator. The camera/illuminator position should        not need adjusting thereafter.

Patient examination:

-   -   1. The patient is seated and asked to place their chin on the        chin rest. The chin rest is adjusted (Z axis) for the comfort of        the patient. The patient is asked to hold their forehead against        the forehead rest.    -   2. The frame holding the camera & illumination is positioned on        the axis of the first eye and brought close enough for rough        focus on the skin.    -   3. The frame is adjusted for vertical and horizontal centering,        and then moved forward for fine focusing.    -   4. The illuminator is adjusted forward and back, and rotated for        best illumination of the eye. Repeat fine focus as necessary.        The patient is asked to look directly at the center or top        center of the camera lens. Instructions are given to the patient        for blinking regimens by the diagnostician. It will be noted        that measurement is taken when the patient is not blinking, but        that this interval is between the previous blink and before the        next blink. Therefore, as employed herein the terms “after        blinking” and “before blinking” are somewhat interchangeable as        they both refer to the substantially non-eyelid moving period of        time “between blinks”.    -   5. The images are viewed and recorded as desired.    -   6. The frame may be pulled away from the patient (to clear the        nose) and moved horizontally to the next eye. Steps 2.-5 are        repeated.

The system could be fully motorized and operated in manual,semi-autonomous, or autonomous modes, depending upon the sophisticationof the control software. A fully automatic system would adjust themechanical stand, focus the camera, record the motion of the lipid film,calculate various measurements of the film structure, report anassessment of the quality of the lipid film, and record the data in thepatient's record file.

The invention having been thus disclosed, diverse changes and variationin the apparatus and method will occur to those skilled in the art, andall such changes and modifications are intended to be within the scopeof the invention, as set forth in the following claims:

1. A method for measuring the thickness of the lipid layer on thesurface of a patient's eye after distribution of the lipid layersubsequent to blinking comprising the steps of: illuminating the lipidlayer of a patient's eye with a broad spectrum light source illuminatorin the visible region and being a lambertian emitter such that the raysfrom the light source are specularly reflected from the lipid layer andundergo constructive and destructive interference in the lipid layerthereby producing interference patterns; and an imaging device forobserving the specularly reflected light such that the interferencepatters on the tear film lipid layer are observable.
 2. The methodaccording to claim 1 wherein the illuminator comprises an arcuateemitter and wherein the surface of the lambertian emitter issubstantially parallel to the surface of the eye.
 3. The methodaccording to claiml wherein the specularly reflected light is observedthrough a hole defining an opening in the illuminator.
 4. The methodaccording to claim 3 wherein the opening in the illuminator allows forobservation of the specularly reflected light from behind saidilluminator.
 5. The method according to claim 3 further including thesteps of collecting and focusing the specularly reflected light and thestep of generating an output signal representative thereof operativelyassociated with the opening.
 6. The method according to claim 5 furtherincluding the step of recording the output signal representative of thespecularly reflected light.
 7. The method according to claim 6 whereinthe step of recording the output signal representative of the specularlyreflected light records in real time.
 8. The method according to claim 5wherein the step of collecting and focusing the output signal isproduced by use of a camera lens system.
 9. The apparatus according toclaim 6 wherein the recording is selected from the group of recordingdevices consisting of computer memory, video cassette recording devices,analog recording devices and digital recording devices.
 10. The methodaccording to claim 1 wherein the specularly reflected light is observedwhen the patient's head is positioned on an observation platform. 11.The method according to claim 2 wherein the arcuate emitter isconstructed and arranged such that the light rays emitted therefromstrike the surface of the eye such that Snell's Law is satisfied andproduces an observable area of interference on the surface of the eye.12. The method according to claim 1 wherein said illuminator furtherincludes a plurality of spaced apart light emitting diodes adapted toemit light in the visible region; and a diffuser for diffusing the lightemitted by the respective light emitting diodes positioned between thelight emitting diodes and the surface of the eye and further, whereinthe diffuser is arcuate such that the light rays emitted therefromstrike the surface of the eye such that Snell's law is satisfied withrespect to the acceptance angle of the camera lens system to produce anobservable area of interference on the eye.
 13. The method according toclaim 11 wherein the light rays that generate the visible viewing areaof interference are substantially normal to the surface of the eye. 14.The method according to claim 1 wherein said illuminator has a totalradiated power of less than 1 W.
 15. A method for measuring thethickness of the lipid layer on the surface of an eye after distributionof the lipid layer subsequent to blinking comprising the steps of:illuminating the lipid layer of a patient's eye with a broad spectrumlight source illuminator in the visible region and being a lambertianemitter such that the light source is specularly reflected from thelipid layer and undergoes constructive and destructive interference inthe lipid layer thereby producing interference patters in the tear filmand further, wherein the total light emitted from the surface of theilluminator is less than 10 μW/mm²; and observing the specularlyreflected light.
 16. The method according to claim 15 wherein theilluminator further includes an arcuate emitter and wherein the surfaceof the emitter is substantially parallel to the surface of the eye. 17.The method according to claim 15 wherein the specularly reflected lightis observed through a hole defining an opening in the illuminator. 18.The method according to claim 17 wherein the opening in the illuminatorallows for observation of the specularly reflected light from behindsaid illuminator.
 19. The method according to claim 17 further includingthe step of collecting and focusing the specularly reflected light andthe step of generating an output signal representative thereofoperatively associated with the opening.
 20. The method according toclaim 19 further including the step of recording the output signalrepresentative of the specularly reflected light.
 21. The methodaccording to claim 20 wherein the step of recording the output signalrepresentative of the specularly reflected light records in real time.22. The method according to claim 19 wherein the steps of collecting andfocusing is produced by the use of a camera lens system.
 23. The methodaccording to claim 20 wherein the step of recording is selected from thegroup of recording devices consisting of computer memory, video cassetterecording devices, analog recording devices and digital recordingdevices.
 24. The method according to claim 15 wherein the specularlyreflected light is observed when the patient's head is positioned on anobservation platform.
 25. The method according to claim 15 wherein thearcuate emitter is constructed and arranged such that the light raysemitted therefrom strike the surface of the eye such that Snell's law issatisfied and an observable area of interference is produced on the eye.26. The method according to claim 15 wherein the illuminator furtherincludes a plurality of spaced apart light emitting diodes adapted toemit light in the visible region; and diffusing the light emitted by therespective light emitting diodes and further, wherein the illuminator isarcuate such that the light rays emitted from the lambertian emitterstrike the surface of the eye such that Snell's law is satisfied withrespect to the acceptance angle of said camera lens system to produce anobservable area of interference on the eye.
 27. The method according toclaim 25 further including the step of collecting the specularlyreflected light and focusing the specularly reflected light generates anoutput signal representative thereof.
 28. The method according to claim25 wherein the illuminator has a total radiated power of less than 1 W.29. The method according to claim 25 wherein the light rays thatgenerate the visible viewing area of interference are essentially normalto the surface of the eye.
 30. A method for measuring the thickness ofthe lipid layer on the surface of a patient's eye after distribution ofthe lipid layer subsequent to blinking comprising the steps of:illuminating the lipid layer of a patient's eye with broad spectrumlight source illuminator in the visible region and being a uniformillumination lambertian emitter such that the light source is specularlyreflected from the lipid layer and undergoes constructive anddestructive interference in the lipid layer; and further wherein theilluminator illuminates the patients face, but wherein only an areabelow the pupil satisfies Snell's law; and observing the area ofinterference in specularly reflected light on the tear film lipid layerbelow the pupil.
 31. The method according to claim 30 further includingthe steps of collecting and focusing the specularly reflected light suchthat the interference patterns on the tear film lipid layer areobservable.
 32. The method according to claim 30 wherein the illuminatorilluminates an area of the patient's eye and wherein the area havingviewable interference fringes is located below the pupil.
 33. The methodaccording to claim 32 wherein the area having viewable interferencefringes is an area of at least 12.5 mm².
 34. The method according toclaim 30 wherein the illuminator has a total illumination intensity ofless than that which would induce reflex tearing or cause aproprioceptive response to occur.
 35. The method according to claim 34wherein the illuminator has a total illumination intensity of betweenabout 1 μW/mm² and 15μW/mm² at the surface of the illuminator.
 36. Themethod according to claim 32 wherein the specularly reflected light isobserved when the patient's head is positioned on an observationplatform.
 37. The method according to claim 30 further including thestep of recording the observable area of interference of the specularlyreflected light.
 38. The method according to claim 37 wherein the stepof recording the observable are of interference records in real time.39. The method according to claim 37 wherein the step of recording isselected from the group of recording devices consisting of computermemory, video cassette recording devices, analog recording devices anddigital recording devices.
 40. The method according to claim 31 whereinthe step of collecting and focusing the specularly reflected lightgenerates an output signal representative thereof.
 41. The methodaccording to claim 30 wherein the illuminator comprises an array oflight emitting diodes and a diffuser positioned between the respectivediode array and the lipid layer of the tear film.
 42. The methodaccording to claim 41 where the diffuser is arcuate such that the lightrays emitted from the lambertian emitter strike the surface of the eyesuch that Snell's law is satisfied and an observable area ofinterference is produced on the eye.
 43. A method for measuring thethickness of the lipid layer on the surface of an eye after distributionof the lipid layer subsequent to blinking comprising the steps of:illuminating the lipid layer of a patient's eye with a broad spectrumlight source illuminator in the visible region and being uniformillumination lambertian emitter such that the light source is specularlyreflected from the lipid layer and undergoes constructive anddestructive interference in the lipid layer and wherein the lightemitted from the illuminator travels directly to the lipid layer withoutreflection and strikes the lipid layer; and collecting and focusing thespecularly reflected light such that the interference patterns on thetear film lipid layer are observable.
 44. The method according to claim43 wherein the illuminator illuminates an area of the patient's eye andwherein the area having viewable interference fringes is located belowthe pupil.
 45. The method according to claim 43 wherein the area havingviewable interference fringes in an area of at least 12.5 mm².
 46. Themethod according to claim 43 wherein the illuminator has a totalillumination intensity of less than what which would induce reflextearing or cause a proprioceptive response to occur.
 47. The methodaccording to claim 43 wherein the illuminator has a total illuminationintensity of between about 1 μW/mm² and 15 μW/mm² at the surface of theilluminator.
 48. The method according to claim 43 wherein theilluminator has a total radiated power of less than about 1 W.
 49. Themethod according to claim 44 wherein the specularly reflected light isobserved when the patient's head is positioned on an observationplatform.
 50. The apparatus according to claim 43 further including thestep of recording the observable area of interference of the specularlyreflected light.
 51. The apparatus according to claim 50 wherein thestep of recording the observable area of interference records in realtime.
 52. The apparatus according to claim 51 wherein the step ofrecording is selected from the group of recording devices selected fromthe group consisting of computer, video cassette recording devices anddigital recording devices.
 53. The method according to claim 44 whereinthe step of collecting and focusing the specularly reflected lightgenerate an output signal representative thereof.
 54. The methodaccording to claim 43 wherein the illuminator comprises an array oflight emitting diodes and a diffuser positioned between the respectivediode array and the lipid layer of the tear film.
 55. The methodaccording to claim 54 where the diffuser is arcuate such that the lightrays emitted from the lambertian emitter strike the surface of the eyesuch that Snell's law is satisfied and an observable area ofinterference is produced on the eye.